Lamellar Liquid Crystalline Phases for Cutaneous Delivery of Paclitaxel: Impact of the Monoglyceride.

MedLine Citation:

PMID:
23135821
Owner:
NLM
Status:
Publisher

Abstract/OtherAbstract:

PURPOSE: To develop liquid crystalline phases with monoglycerides, and assess whether the monoglyceride type favors cutaneous over transdermal paclitaxel delivery. METHODS: BRIJ-based lamellar phases were prepared with 0.5% paclitaxel and 20% of either monocaprylin (LP-MC), monomyristolein (LP-MM) or monoolein (LP-MO). Skin electrical resistance, drug release and cutaneous delivery in vitro and in vivo were assessed. Viability of skin equivalents and release of IL-1α were assessed as indexes of irritation potential. RESULTS: An inverse relationship between monoglyceride acyl chain length and amount of paclitaxel delivered was observed. Although the largest paclitaxel amounts were delivered by LP-MC, all formulations delivered higher levels of drug in the skin (56-64-fold) than across the tissue. The superiority of LP-MC seems related to a stronger decrease in skin resistance (as an index of permeability), and not to increased drug release. LP-MC displayed similar penetration-enhancing ability in vivo, and a much lower irritation potential than Triton-X100 (a moderate irritant), leading to 3-fold higher skin equivalent viability and release of 60-fold less IL-1α. CONCLUSIONS: Even though LP-MC delivered the largest amounts of paclitaxel, all formulations provided similar cutaneous/transdermal delivery ratios, suggesting that changing the monoglyceride acyl chain length did not affect the balance between cutaneous and transdermal delivery.